The primary goal of research outlined in this proposal is the continued development of general, stereocontrolled annulation approaches to highly functionalized seven- and eight-membered rings. Readily accessible synthons have been designed to allow conversion to carbocycles and heterocycles bearing different substitution patterns and stereochemistries. Control of stereochemistry and regiochemistry is proposed to be established by a novel mechanistic pathway which has high predictability and reliability. This permits unprecedented control in conversion of acyclic synthons to important carbocycles and heterocycles. A natural evolution of this program is the application of these exciting and important new synthetic methods to the total synthesis of complex organic molecules. Several challenging target structures have been put forward which will be constructed in order to demonstrate the value of these synthetic methods. Included are approaches to dactylol, furanether B, and the eunicellin/cladiellin class of diterpenes. The latter possess particular importance in health related fields. Many unique, highly oxygenated cembranoids have recently been isolated and fully characterized. Much less common are bicyclic cembranoids in which a transannular C-C bond is formed across the cembrane skeleton. Of this group, the eunicellin class of gorgonian and alcyonarian metabolites are the best represented. The eunicellin skeleton is present in several known natural products, including eunicellin, cladiellin, the asbestinins, and the sclerophytins. The latter materials have exhibited promising cytotoxic activity against a variety of cancerous cell lines. No efforts directed towards the total synthesis of these novel compounds have been reported. It is suggested that the eunicellin ring system may be accessed by the annulation strategy outlined in this proposal, leading to enantioselective syntheses of cladiellin and sclerophytin B. Finally, an approach to a skeletal substructure of the antineoplastic compound taxol is also outlined.